Adenosinergic modulation of respiratory neurones and hypoxic responses in the anaesthetized cat

1. The modulatory effects of intracellularly injected adenosine on membrane potential, input resistance and spontaneous or evoked synaptic activity were determined in respiratory neurones of the ventral respiratory group. 2. The membrane potential hyperpolarized and sometimes reached values which were beyond the equilibrium potential of Cl(-)-dependent IPSPs. At the same time, neuronal input resistance decreased. 3. Spontaneous and stimulus-evoked postsynaptic activities were decreased, as were mean respiratory drive potentials. 4. Systemic injection of the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.01-0.05 mg kg-1) resulted in an increase in mean peak phrenic nerve activity when arterial chemoreceptors were denervated. In contrast, phrenic nerve activity decreased when arterial chemoreceptors were left intact. 5. The depressant effect of adenosine on synaptic activity was abolished after systemic DPCPX administration. DPCPX caused an increase in respiratory drive potentials, increased the amplitude of stimulus-evoked IPSPs, and hyperpolarized membrane potential. 6. Administration of DPCPX blocked the early hypoxic depression of stimulus-evoked IPSPs, doubled the delay of onset of hypoxic apnoea and shortened the time necessary for recovery of the respiratory rhythm. 7. The data indicate that adenosine acts on pre- and postsynaptic A1 receptors resulting in postsynaptic membrane hyperpolarization and depression of synaptic transmission. Blockade of A1 receptors increases respiratory activity, indicating that adenosine A1 receptors are tonically activated under control conditions. Further activation contributes to the hypoxic depression of synaptic transmission in the respiratory network.